• Zhe Xu and Bin Qian.
• Anesthesia Surgery Center, Chinese PLA General Hospital, Beijing, 100853, China.
• Neurosci. Lett. 2020 Mar 16; 721: 134785.

AbstractPostoperative cognitive dysfunction in elderly patients has been related to neurodegenerative disorders and mortality. Sevoflurane anesthesia has been implicated in both postoperative cognitive dysfunction and neurotoxicity. Given the advantages of using inhaled anesthetics like sevoflurane, it is important to understand how their usage results in neurotoxicity and subsequently devise ways to circumvent or attenuate the anesthetic-mediated induction in neurotoxicity. We have used an aged rat model to investigate the molecular mechanisms by which sevoflurane inhalation results in neurotoxicity and whether modulation of these molecular mechanisms can inhibit or attenuate neurotoxicity and cognitive learning and memory impairment in these animals. Low- or high-dose of sevoflurane resulted in reactive oxygen species generation, increased NADPH oxidase protein expression, apoptosis and autophagy. Sevoflurane inhalation resulted in significant inhibition of brain derived neurotrophic factor (BDNF) and cognitive impairment. And the activation of PI3K/Akt/mTOR signaling pathways are attenuated in sevoflurane-mediated anesthesia. Adeno-associated virus (AAV)-mediated expression of Bdnf, but not controls EGFP, attenuated sevoflurane-induced oxidative stress and cognitive impairment in the rats. Our results highlight that AAV-mediated gene therapy might offer a potential therapeutic opportunity to treat post-operative cognitive impairment resulting from inhaled anesthetics.Copyright © 2020 Elsevier B.V. All rights reserved.

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